Impaired memory is an important component of diseases such as Alzheimer?s disease, temporal lobe epilepsy, depression, and schizophrenia that collectively affect over twenty million Americans. Our long-range goal is to contribute to a better understanding of the neural mechanisms that underlie memory processes, in order to bring us closer to developing new therapies for these disabled patients. The objective of this proposal is to characterize neural signals that support a prototypical form of memory, recognition memory. Recognition memory is the ability to perceive a recently encountered item as familiar. This ability is impaired following lesions of medial temporal lobe structures, including the hippocampus and the underlying perirhinal and entorhinal cortices. Neural signals that may support recognition memory have been described in the perirhinal and entorhinal cortices. However, despite extensive research, there is currently little evidence for the existence of recognition memory signals in the non-rodent hippocampus. This apparent inconsistency between the findings from lesion and physiology studies fuels a current controversy regarding the contribution of the hippocampus to recognition memory and prevents a full understanding of the organization of memory. Based on preliminary data, we hypothesize that single neurons, the local field potential (LFP), and synchronized ensembles of neurons in the hippocampus display modulations in activity that may be used for recognition memory. The experiments proposed here will directly test this hypothesis, using multi-electrode recordings of spiking activity and LFPs during a recognition memory task. We will examine modulations in single-unit firing rates, amplitude and power in the LFP, and spike-field neuronal synchronization with respect to performance on the Visual Preferential Looking Task, which is known to be highly sensitive to lesions of the hippocampus. The proposed experiments have the following potential outcomes: to resolve the apparent inconsistency between lesion and neurophysiological studies regarding the role of the hippocampus in recognition memory;to determine the functional significance of oscillatory activity, including theta-band oscillations, in the hippocampus;and to identify neuronal synchronization as a potential mechanism underlying memory formation. PUBLIC HEALTH RELEVANCE Impaired memory is an important component of diseases such as Alzheimer's disease, temporal lobe epilepsy, depression, and schizophrenia that collectively affect over twenty million Americans. Our long-range goal is to contribute to a better understanding of the neural mechanisms that underlie memory processes, in order to bring us closer to developing new therapies for these disabled patients. The objective of this proposal is to identify neural mechanisms in the hippocampus and subjacent cortex that may underlie memory formation.